INDICATION AND IMPORTANT SAFETY INFORMATION FOR ULTANE^® (sevoflurane)

INDICATION¹

ULTANE® (sevoflurane) is indicated for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery. ULTANE should be administered only by persons trained in the administration of general anesthesia. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available. Since level of anesthesia may be altered rapidly, only vaporizers producing predictable concentrations of ULTANE should be used.

IMPORTANT SAFETY INFORMATION¹

• ULTANE can cause malignant hyperthermia. Postmarketing reports of malignant hyperthermia, some of which have been fatal, have occurred. ULTANE should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents, or in patients with known or suspected susceptibility to malignant hyperthermia.
• Findings taken from patient and animal studies suggest that there is a potential for renal injury when ULTANE is used at low flow rates, which is presumed due to Compound A. The level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established. To minimize exposure to Compound A, ULTANE exposure should not exceed 2 MAC-hours at flow rates of 1 to <2 L/min. Fresh gas flow rates <1 L/min are not recommended.
• Because clinical experience in administering ULTANE to patients with renal insufficiency (creatinine >1.5 mg/dL) is limited, its safety in these patients has not been established.
• ULTANE may be associated with glycosuria and proteinuria when used for long procedures at low flow rates.
• KOH containing CO₂ absorbents are not recommended for use with ULTANE. An exothermic reaction occurs when ULTANE is exposed to CO₂ absorbents. This reaction is increased when the absorbent becomes desiccated. Rare cases of extreme heat, smoke, and/or spontaneous fire have been reported during ULTANE use in conjunction with the use of desiccated CO₂ absorbent, specifically those containing potassium hydroxide (e.g., Baralyme).
• Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering ULTANE to susceptible patients (e.g. patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).
• Rare increases in serum potassium resulting in cardiac arrhythmias and death have been noted in pediatric patients during the postoperative period following the use of inhaled anesthetic agents. Contributing risk factors appear to be latent or overt neuromuscular disease, particularly Duchenne muscular dystrophy. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. Early, aggressive intervention to treat both hyperkalemia and resistant arrhythmias, and subsequent evaluation for latent neuromuscular disease, is recommended.
• Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in the third trimester of gestation through the first three years of age may result in adverse cognitive or behavioral effects on their developing brains. The studies in children have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors, such as the surgery or underlying illness. Anesthetic and sedation drugs are a necessary part of the care of children when needed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.
• Due to ULTANE’s insolubility in blood, hemodynamic changes may occur more rapidly than with other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of ULTANE.
• Seizures have been reported in association with ULTANE use, the majority of which have occurred in children and young adults, most of whom had no predisposing risk factors. Clinical judgment should be exercised when using ULTANE in patients who may be at risk for seizures.
• Drug interactions: Benzodiazepines and opioids would be expected to decrease the MAC of ULTANE. The anesthetic requirement for ULTANE is decreased when administered in combination with nitrous oxide. ULTANE increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants.
• Very rare cases of mild, moderate, and severe postoperative hepatic dysfunction or hepatitis with or without jaundice have been reported from postmarketing experiences. In addition, rare postmarketing reports of hepatic failure and hepatic necrosis have been associated with the use of ULTANE. Clinical judgment should be used in patients with underlying hepatic conditions or who are under treatment with drugs known to cause hepatic dysfunction. It has been reported that previous exposure to halogenated hydrocarbon anesthetics may increase the potential for hepatic injury.
• Adverse events reported by ≥5% of the surgical patients receiving ULTANE during clinical trials during induction included: bradycardia, tachycardia, agitation, laryngospasm, airway obstruction, breathholding, and increased cough; during maintenance and emergence: shivering, hypotension, bradycardia, somnolence, agitation, nausea, vomiting, and increased cough were reported.
  

Please see the full Prescribing information for ULTANE.
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Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR NIMBEX^® (cisatracurium besylate)

INDICATION²

NIMBEX^® (cisatracurium besylate) is indicated as an adjunct to general anesthesia to facilitate tracheal intubation in adults and in pediatric patients 1 month to 12 years of age; to provide skeletal muscle relaxation in adults during surgical procedures or mechanical ventilation in the ICU; and to provide skeletal muscle relaxation during surgical procedures via infusion in pediatric patients 2 years and older. NIMBEX is not recommended for rapid sequence endotracheal intubation.

IMPORTANT SAFETY INFORMATION²

• NIMBEX is contraindicated in patients with known hypersensitivity to cisatracurium; severe anaphylactic reactions have been reported. The use of 10-mL NIMBEX multiple-dose vials is contraindicated in pediatric patients less than 1 month of age and low birth-weight infants because the formulation contains benzyl alcohol.
• NIMBEX has been associated with residual paralysis; patients with neuromuscular disease and carcinomatosis may be at higher risk. A lower maximum initial bolus is recommended in these patients to prevent complications.
• Serious and fatal adverse reactions including “gasping syndrome,” which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations, can occur in neonates and infants treated with benzyl alcohol–preserved drugs, including NIMBEX 10-mL multiple-dose vials. Single-use vials (5-mL and 20-mL) of NIMBEX do not contain benzyl alcohol.
• Laudanosine, an active metabolite of NIMBEX, has been shown to cause seizures in animals. NIMBEX-treated patients with renal or hepatic impairment may have higher metabolite concentrations (including laudanosine) than patients with normal renal and hepatic function. Patients with renal or hepatic impairment receiving extended administration of NIMBEX may be at higher risk of seizures. The level of neuromuscular blockade during long-term NIMBEX administration should be monitored with a nerve stimulator to titrate NIMBEX administration to the patient’s needs and limit exposure to toxic metabolites.
• Severe hypersensitivity reactions to NIMBEX have been reported, including life-threatening and fatal anaphylactic reactions. There have been reports of wheezing, laryngospasm, bronchospasm, rash, and itching following NIMBEX administration in pediatric patients. Precaution should be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents.
• Confirm proper selection of intended product, avoid confusion with other injectable solutions, and ensure that the intended dose is clearly labelled and communicated. Administration of NIMBEX results in paralysis, which may lead to respiratory arrest and death, a progression that may be more likely to occur in a patient for whom it is not intended.
• Neuromuscular blockade in the conscious patient can lead to distress. Use NIMBEX in the presence of appropriate sedation or general anesthesia. Monitor patients to ensure that the level of anesthesia is adequate.
• The 20-mL vial of NIMBEX is intended only for administration as an infusion for use in a single patient in the ICU. It should not be used multiple times because it does not contain a preservative, and there is a higher risk of infection.
• Certain drugs may enhance the neuromuscular blocking action of NIMBEX, including inhalational anesthetics, antibiotics, magnesium salts, lithium, local anesthetics, procainamide, and quinidine. Acid-base and/or serum electrolyte abnormalities may potentiate the action of neuromuscular blocking agents. Shorter durations of neuromuscular block may occur and NIMBEX infusion rate requirements may be higher in patients chronically administered phenytoin or carbamazepine. Use peripheral nerve stimulation and monitor clinical signs of neuromuscular blockade to determine adequacy of neuromuscular blockage and the need to adjust the NIMBEX dosage.
• NIMBEX has not been studied in patients susceptible to malignant hyperthermia (MH). Because MH can develop in the absence of established triggering agents, the clinician should be prepared to recognize and treat MH in any patient undergoing general anesthesia.
• The use of succinylcholine prior to NIMBEX may decrease the time to onset of maximum neuromuscular blockade but has no effect on the duration. Administration of inhalational anesthetics with nitrous oxide/oxygen for greater than 30 minutes to achieve 1.25 MAC may prolong the duration of action of initial and maintenance doses of NIMBEX. This may potentiate the neuromuscular blockade.
• Adverse reactions reported by <1% of the surgical patients treated with NIMBEX during clinical trials include bradycardia, hypotension, flushing, bronchospasm, and/or rash.
• Adverse reactions occurred among the 68 adult ICU patients who received NIMBEX in conjunction with other drugs in US and European clinical studies. One out of 68 patients experienced bronchospasm. In one study, there were 2 reports of prolonged recovery among 28 patients administered NIMBEX compared with 13 reports among 30 patients administered vecuronium.

Please see the full Prescribing information for NIMBEX.
You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

This website and the information contained herein is intended for use by US Healthcare Professionals only and is provided for informational purposes only.

References: 1. ULTANE [package insert]. North Chicago, IL: AbbVie Inc. 2. NIMBEX [package insert]. North Chicago, IL: AbbVie Inc.